This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California Mucositis of the alimentary tract (AT) is a debilitating side effect of cancer therapies in a high percentage of patients receiving chemotherapy, bone marrow transplantation, and high-dose radiation to the head and neck.Recent studies from our laboratory have isolated a new population of stem cells from human gingiva, an easily accessible tissue source, namely GMSC, which exhibit not only multipotent differentiation and self-renewal capacities, but also possess distinct immunomodulatory functions. Cell-based therapy with GMSC significantly ameliorated both clinical and histopathological severities of the colonic inflammation in the experimental murine colitis, presumably by suppressing inflammatory infiltrates, specifically interleukin-17 (IL-17) secreting cells, and a myriad of inflammatory cytokines/mediators, and recruiting regulatory T cells (Tregs) at the colonic sites. In another disease model of mucosal inflammation induced by chemotherapy, we observed a significant reversal of AT mucositis and regain of body weight in nearly 100% of mice undergoing an exploratory one dose treatment with GMSC Experimental Approaches: We will examine the immunomodulatory effects of GMSC on Treg and Th17 functions and how they contribute to mucositis using both in vitro and in vivo studies. Optical coherence tomography (OCT) coupled with multiphoton microscopy (MMP) technology will be utilized to decipher stem cell homing to mucositic sites. We will test whether adaptive transfer with Pan-T cells, ex vivo expanded Tregs, and pharmacologic immune boosting therapies can reverse mucosal injuries.